The Survival Advantage of Females at Premenopausal Age Is Race Dependent in Colorectal Cancer

Background. A female prognostic advantage in younger individuals has been demonstrated in various cancers. Several large-scale analyses based on different racial backgrounds have reported inconsistent results in colorectal cancer. The aim of the present study was to evaluate the prognostic value of sex and age in patients with colorectal cancer of different ethnic groups. Methods. We identified 71,812 eligible patients from the Surveillance, Epidemiology and End Results database. According to age at diagnosis, the patients were categorized into premenopausal age (≤45 yrs), menopausal age (46–54 yrs), and postmenopausal age (≥55 yrs) subgroups for further analysis. Results. Multivariate analysis identified the female survival advantage to be significant in the premenopausal age subgroup ( P = 0.002 , HR (95% CI): 0.73 (0.60–0.89)), diminished in the menopausal age subgroup ( P = 0.09 ), and absent in the postmenopausal age subgroup ( P = 0.96 ). Furthermore, the female survival advantage at premenopausal age was significant only in white patients ( P = 0.001 , HR (95% CI): 0.68 (0.54–0.87)) and not in either American Indian/Alaska Native or Asian or Pacific Islander patients. There was a trend of better survival of females in black patients ( P = 0.07 ). Conclusions. Sex was a major prognostic factor in colorectal cancer patients, especially premenopausal women, and the difference was also associated with race.

Download Full-text

UGT1As polymorphisms predict toxicity in colorectal cancer patients treated with different recommended doses of irinotecan oriented by UGT1A1*28 polymorphism based on previous phase I study

Journal of Clinical Oncology ◽

10.1200/jco.2007.25.18_suppl.14511 ◽

2007 ◽

Vol 25 (18_suppl) ◽

pp. 14511-14511 ◽

Cited By ~ 1

Author(s):

S. Hazama ◽

H. Koudo ◽

S. Yoshida ◽

R. Shimizu ◽

H. Ozasa ◽

...

Keyword(s):

Colorectal Cancer ◽

Maximum Tolerated Dose ◽

Wild Type ◽

Eligibility Criteria ◽

Metastatic Lesions ◽

Significant Difference ◽

The Difference ◽

Colorectal Cancer Patients ◽

Previous Phase ◽

Written Informed Consent

14511 Background: We have presented at 2006 ASCO annual meeting about a genetic UGT1A1 polymorphism oriented phase (P) I study of Irinotecan and 5’-DFUR for metastatic colorectal cancer (MCRC) to determine the maximum tolerated dose (MTD) and the recommend doses (RD) for each UGT1A1 *1/*1 and *1/*28 genotypes. The RD of biweekly Irinotecan administration was 150 mg/m2 for patients (pts) with wild *1/*1 genotype and 70 mg/m2 of Irinotecan for mutated *1/*28. Now we are carrying out a *28 oriented P II study based on this RD. Here we report the profiles of toxicities in the P II study of irinotecan and 5’-DFUR to analyze other kinds of UGT1As polymorphisms in relation to irinotecan toxicities. Patients & Methods: Eligibility criteria were as follows; histologically proven CRC with unresectable metastatic lesions, PS 0–1, age<76, adequate organ functions, and written informed consent. Twenty one pts with wild type genotype and 9 pts with mutated genotype were enrolled. Irinotecan was infused 150 mg/m2 for pts with *1/*1 genotype and 70 mg/m2 for *1/*28. Hematological and non-hematological toxicities were graded, and UGT1As polymorphisms (UGT1A1*6 and *7, UGT1A7*1*2*3*4, UGT1A9*22) were analyzed. Results: Grade (G)3 & 4 toxicities were observed in 6 of 22 (27%) wild type pts and in 3 of 9 (33%) mutated pts, and in 9 of 31 (29%) all pts. There was no significant difference on the profiles of toxicities between the pts with wild genotype and mutated genotype, irrespective of the difference of the quantity of irinotecan. So, the RD was thought to be adequate. In pts with UGT1A1*6 allele, G3 & 4 toxicities were observed 6/11 (55%), on the other hand 3/20 (15%) in pts without *6 allele (p=0.038). G3 & 4 toxicities were also more frequent in pts with UGT1A7*3 alleles than pts without *3 allele (p<0.10). Conclusions: The profiles of toxicities of pts with *1/*1 or *1/*28 genotypes were similar irrespective of the difference of the quantity of irinotecan. The result indicated that the RD of latest PI for each group was adequate, and this P II study is suitable to analyze other kinds of polymorphisms that have correlation to irinotecan toxicities. UGT1A1*6 and UGT1A7*3 allele will be a novel predictor for toxicity of irinotecan. No significant financial relationships to disclose.

Download Full-text

The correlation of thrombin-activated fibrinolysis inhibitor (TAFI) levels and clinicopathologic factors in advanced colorectal cancer patients

Journal of Clinical Oncology ◽

10.1200/jco.2009.27.15_suppl.e22217 ◽

2009 ◽

Vol 27 (15_suppl) ◽

pp. e22217-e22217

Author(s):

T. Salman ◽

A. Bilici ◽

B. O. Ustaalioglu ◽

M. Seker ◽

B. Sonmez ◽

...

Keyword(s):

Colorectal Cancer ◽

Prognostic Factors ◽

Cancer Patients ◽

Large Scale ◽

Performance Status ◽

Blood Levels ◽

Thromboembolic Events ◽

Fibrinolysis Inhibitor ◽

Clinicopathologic Factors ◽

Colorectal Cancer Patients

e22217 Background: There are many ongoing researchs for novel prognostic factors in colorectal cancers. Increased thromboembolic events were associated with poor prognosis and survival in cancer patients. Thrombin-activated fibrinolysis inhibitor (TAFI), which has inhibitory effects on fibrinolysis, was proven to play a major role in hypercoagulopathy and was reported to reach high blood levels in cancer patients compared to those in the general population. Methods: TAFI levels were measured. The correlation between those levels and clinicopathologic features were analyzed in 82 patients with advanced stage colorectal cancer receiving treatment in our clinic. Results: Eighty-two patients were evaluated. Patients characteristics included 54 males (65.9%), 28 females (34.1%); median age 56.4 (range:24–76). The mean TAFI levels was 198,36±70,01 Ğer yazali and TAFI levels were found to be high in 70% of patients. High levels of TAFI were more common in rectum cancer patients compared with colon cancer patients. There was no significant correlation between TAFI levels and clinicopathologic factors, such as age, sex, body mass index, performance status, number of metastases, grade, vascular invasion, perineural invasion and CEA levels. The TAFI levels of patients receiving bevacizumab (202.1±66.6) were more higher than those no receiving (191,83±76,21), but this association was not statistically significant (p>0.05). Conclusions: Although the statistical analysis proved insignificant in our study, the effect of thromboembolic events on prognosis and survival is well established. Thus, large scale prospective studies are required to determine prognostic factors. No significant financial relationships to disclose.

Download Full-text

Patterns of osteoporosis (OP) in survivors of colorectal cancer (CRC) enrolled on SWOG trials.

Journal of Clinical Oncology ◽

10.1200/jco.2017.35.15_suppl.10056 ◽

2017 ◽

Vol 35 (15_suppl) ◽

pp. 10056-10056

Author(s):

Afsaneh Barzi ◽

Dawn L. Hershman ◽

Cathee Till ◽

Heinz-Josef Lenz ◽

Howard S. Hochster ◽

...

Keyword(s):

Colorectal Cancer ◽

Fracture Risk ◽

Cancer Patients ◽

Phase Iii ◽

P Value ◽

National Hospital Discharge Survey ◽

Prostate Cancer Prevention ◽

The Difference ◽

Using Data ◽

Colorectal Cancer Patients

10056 Background: There are currently 1.5 million CRC survivors in US and this number will continue to rise with advancements in treatment. The risk of OP in CRC survivors has not been well described. Methods: We used data from 3 SWOG CRC treatment trials, all of which were phase III and had long term follow-up. Enrollees were linked to Medicare claim files for identification of OP and fractures using HCPCS and ICD9 codes. First, we compared patterns of osteoperosis and fracture risk by sex in colorectal cancer patients. To assess whether patterns of fracture risk by sex differed between patients with vs. without colorectal cancer, we compared the difference in fracture risk by sex in colorectal cancer patients to the difference in fracture risk by sex in the general U.S. population, using data from the National Health Interview Survey (NHIS) and the National Hospital Discharge Survey (NHDS). Finally, we assessed whether absolute estimates of osteoperosis and fracture risk differed between men with colorectal cancer and men without colorectal cancer. Comparison data for men without colorectal cancer were obtained from the placebo arm of the Prostate Cancer Prevention trial (PCPT). Results: We linked 1233 CRC cases with Medicare claims. The median age at CRC diagnosis was marginally higher for women (65 vs 64 ys, p = 0.03). 47% of females, 15% of men with CRC, and 19% of men without CRC had a OP diagnosis. The female to male ratio of osteoporotic fracture in general U.S. population was 1.67, while the same ratio in CRC survivors was 2.84, an increase of 70% (p-value < 0.001). Conclusions: Our study indicates that the risk disparity for OP fracture for females is much greater in CRC survivors than in the general U.S. population. This may be due to more OP diagnoses for female CRC survivors, but not for male CRC survivors.

Download Full-text

Plasminogen Activators in the Intestine of Patients with Inflammatory Bowel Disease

Thrombosis and Haemostasis ◽

10.1055/s-0038-1647042 ◽

1988 ◽

Vol 60 (02) ◽

pp. 262-266 ◽

Cited By ~ 22

Author(s):

P A F de Bruin ◽

G Crama-Bohbouth ◽

H W Verspaget ◽

J H Verheijen ◽

G Dooijewaard ◽

...

Keyword(s):

Colorectal Cancer ◽

Inflammatory Bowel Disease ◽

Bowel Disease ◽

Plasminogen Activators ◽

Intestinal Tissue ◽

Colonic Adenomas ◽

Tissue Plasminogen ◽

Inflammatory Bowel ◽

The Difference ◽

Colorectal Cancer Patients

SummaryPlasminogen activators were determined in intestinal tissue, obtained after surgery from patients with Crohn’s disease and ulcerative colitis, and compared with normal intestinal tissue from colorectal cancer patients.The activity and quantity of tissue-plasminogen activator (t-PA) was found to decrease with the severity of inflammation in the patients with inflammatory bowel disease. Urokinase (u-PA) activity, however, was not changed compared with controls or in relation with severity of inflammation. In contrast, the level of u-PA antigen was found to be increased significantly in the inflammatory bowel disease tissues and was also related with severity of inflammation. The difference between u-PA activity and antigen in inflammatory bowel disease tissue could be attributed to an increase in inactive pro-u-PA and u-PA-inhibitor complexes.This increase in u-PA and the concomitant decrease in t-PA, are similar to those found in premalignant colonic adenomas, and might be related to the known increased cancer risk in inflammatory bowel disease.

Download Full-text

KDML: a machine-learning framework for inference of multi-scale gene functions from genetic perturbation screens

10.1101/761106 ◽

2019 ◽

Cited By ~ 1

Author(s):

Heba Z. Sailem ◽

Jens Rittscher ◽

Lucas Pelkmans

Keyword(s):

Colorectal Cancer ◽

Machine Learning ◽

Large Scale ◽

Ad Hoc ◽

Olfactory Receptors ◽

Functional Enrichment ◽

Learning Framework ◽

Gene Functions ◽

Health And Disease ◽

Colorectal Cancer Patients

AbstractCharacterising context-dependent gene functions is crucial for understanding the genetic bases of health and disease. To date, inference of gene functions from large-scale genetic perturbation screens is based on ad-hoc analysis pipelines involving unsupervised clustering and functional enrichment. We present Knowledge-Driven Machine Learning (KDML), a framework that systematically predicts multiple functions for a given gene based on the similarity of its perturbation phenotype to those with known function. As proof of concept, we test KDML on three datasets describing phenotypes at the molecular, cellular and population levels, and show that it outperforms traditional analysis pipelines. In particular, KDML identified an abnormal multicellular organisation phenotype associated with the depletion of olfactory receptors and TGFβ and WNT signalling genes in colorectal cancer cells. We validate these predictions in colorectal cancer patients and show that olfactory receptors expression is predictive of worse patient outcome. These results highlight KDML as a systematic framework for discovering novel scale-crossing and clinically relevant gene functions. KDML is highly generalizable and applicable to various large-scale genetic perturbation screens.

Download Full-text

Derajat Toksisitas Hemoglobin Pada Penderita Kanker Kolorektal Yang Mendapat Kemoterapi CapeOX

ARTERI : Jurnal Ilmu Kesehatan ◽

10.37148/arteri.v1i4.86 ◽

2020 ◽

Vol 1 (4) ◽

pp. 299-305

Author(s):

Yusmaidi ◽

Jordy Oktobiannobel ◽

Muhammad Nur ◽

Bella Sabila Dananda

Keyword(s):

Colorectal Cancer ◽

Cancer Patients ◽

The United States ◽

Hematological Toxicity ◽

P Value ◽

Chemotherapy Drugs ◽

Number Of Patients ◽

Significant Difference ◽

The Difference ◽

Colorectal Cancer Patients

Advances in the treatment and use of chemotherapy have been shown to improve the life expectancy rate for colorectal cancer patients. Studies conducted in China and Hongkong have shown that CapeOX combination chemotherapy regimens are more commonly used than in Europe and the United States. However, the use of chemotherapy drugs containing oxaliplatin and capecitabine can cause side effects such as hematological toxicity, which is one of them is anemia. This study aims to determine the difference in the form of a decrease in the average levels of hemoglobin and the degree of hemoglobin toxicity in colorectal cancer patients undergoing CapeOX chemotherapy. The Design in this study is a historical (retrospective) cohort. This study sample was 70 colorectal cancer patients who received CapeOX chemotherapy for 6 cycles at RSUD Dr. H. Abdul Moeloek in 2018-2019. Consecutive sampling is used in the sampling method. The statistical analysis is using Paired T-Test. There is a significant difference in the average hemoglobin level of colorectal cancer patients (p-value = <0.005), which receive CapeOX chemotherapy for 6 cycles. Besides, there is an increase in the number of patients who get hemoglobin toxicity and the chemotherapy cycle. In the first cycle, 59 patients (84.3%) got hemoglobin toxicity after chemotherapy, and the number continued to increase to 69 patients (98.6%) in the sixth cycle. There was a decrease in hemoglobin levels in colorectal cancer patients who received CapeOX chemotherapy with p-value = <0.05 and increased patients who got hemoglobin toxicity.

Download Full-text

FBXW7 Mutation Analysis and its Correlation with Clinicopathological Features and Prognosis in Colorectal Cancer Patients

The International Journal of Biological Markers ◽

10.5301/jbm.5000125 ◽

2015 ◽

Vol 30 (1) ◽

pp. 88-95 ◽

Cited By ~ 19

Author(s):

Chia-Chu Chang ◽

Hung-Hsin Lin ◽

Jen-Kou Lin ◽

Chun-Chi Lin ◽

Yuan-Tzu Lan ◽

...

Keyword(s):

Colorectal Cancer ◽

Large Scale ◽

Strong Association ◽

Suppressor Gene ◽

Stage I ◽

Wild Type ◽

Tumor Tissues ◽

Patient Prognosis ◽

Colorectal Cancer Patients ◽

Clinicopathological Variables

Purpose This study aimed to determine the prognostic value of mutations in the tumor suppressor gene FBXW7 for clinical outcomes in colorectal cancer (CRC). Methods Between January 2000 and December 2009, FBXW7 mutations in tumor tissues from 1,519 CRC patients at Taipei Veterans General Hospital were assessed using a MassArray system. We compared the clinicopathological variables and prognosis between the wild-type and mutant tumor tissue groups. Results FBXW7 mutations were present in 114/1,519 CRC patients (7.5%). In stage I/II CRC patients, mutant FBXW7 was more common than wild-type FBXW7 (62.3% vs. 50.8%). CRC patients with FBXW7 mutations did not differ significantly in their 5-year overall survival (OS). Stage I/II CRC patients with FBXW7 mutations had lower OS, but this difference was not significant (71.6% vs. 78.2%). Among FBXW7 tumors, S582L was the most frequent mutation type (19.3%), followed by R465H (16.6%), R505C (14.9%) and R479Q (14.9%). Subgroup analysis of FBXW7 mutants showed that R465H/R465C/R479Q had better 5-year OS than other mutant types (76.9% vs. 56.0%; p=0.012). Conclusions There was no strong association between patient prognosis and FBXW7 mutations in our large-scale study.

Download Full-text

Survival After Combined Hepatic Metastasectomy and Chemotherapy in Patients with Concurrent Hepatic and Extrahepatic Colorectal Metastases: A SEER Database Analysis.

10.21203/rs.3.rs-42706/v1 ◽

2020 ◽

Author(s):

Inas Uthman ◽

Ahmed M Fouad ◽

Islam Khaled ◽

Ihab S. Ahmed ◽

Mohammed Faisal

Keyword(s):

Colorectal Cancer ◽

Sigmoid Colon ◽

Alaska Native ◽

Cox Regression ◽

Hepatic Metastases ◽

Colorectal Metastases ◽

Seer Database ◽

Kaplan Meier ◽

The Us ◽

Colorectal Cancer Patients

Abstract Purpose: Colorectal cancer is the second leading cause of death among all cancers worldwide. Hepatic metastases exist in about 50% of colorectal cancer patients. The purpose of this study was to assess the effect of combined hepatic metastasectomy and chemotherapy on the overall survival in patients with concurrent hepatic and extra-hepatic disease.Methods: 2533 patients from the US Surveillance, Epidemiology, and End Results (SEER) database with concurrent colorectal liver metastasis (CRLM) and extra-hepatic disease (EHD) between January 1, 2010, and December 31, 2014, were retrieved. Survival analysis with Kaplan-Meier and Cox-regression was performed to assess the effect of combined hepatic metastasectomy and chemotherapy on 5-year survival. Results: Two-hundred and fourteen (8.4%) patients underwent combined hepatic metastasectomy and chemotherapy. The median survival time among patients underwent combined hepatic metastasectomy, and chemotherapy was significantly higher than chemotherapy alone (24 vs. 21 months; p < 0.0001). Furthermore, older age at diagnosis (≥ 60 years), American Indian/Alaska Native race, primary sites at the recto-sigmoid colon, sigmoid colon, and descending colon, grade III, and the presence of bone metastases were all significantly associated with higher 5-year mortality. Patients who underwent combined hepatic metastasectomy and chemotherapy were significantly associated with 22.2% less 5-year mortality compared to patients who received chemotherapy alone. Conclusion: Combined hepatic metastasectomy with chemotherapy in CRLM patients with EHD yields better survival than chemotherapy only.

Download Full-text

Nuclear factor kB (NF-kB) may predict efficacy of cetuximab therapy in EGFR-positive colorectal cancer

Journal of Clinical Oncology ◽

10.1200/jco.2007.25.18_suppl.14036 ◽

2007 ◽

Vol 25 (18_suppl) ◽

pp. 14036-14036

Author(s):

M. Scartozzi ◽

I. Bearzi ◽

C. Pierantoni ◽

A. Mandolesi ◽

F. Loupakis ◽

...

Keyword(s):

Colorectal Cancer ◽

Progressive Disease ◽

Response Rate ◽

Complete Response ◽

Time To Progression ◽

The Difference ◽

Colorectal Cancer Patients ◽

Cetuximab Therapy ◽

Downstream Signalling Pathway ◽

Colorectal Tumours

14036 Background: NF-kB is part of the aberrant activation of the EGFR-downstream signalling pathway in colorectal tumours, which is described to be inhibited by anti-EGFR therapies. Methods: We retrospectively analysed nuclear immunoreactivity for NF-kB with the aim to determine a correlation between NF-kB expression and outcome in terms of response rate and time to progression in EGFR-positive advanced colorectal cancer patients receiving cetuximab and irinotecan. Results: To date 67 patients (40 males and 27 females, median age 62, range 38–78) were analysed. Cetuximab and irinotecan were administered as a second-line in 18 cases (27%) and after = 3 lines of chemotherapy in the remaining 49 patients (63%). Among the 56 patients evaluable for response we observed a partial (PR) or a complete response (CR) in 10 and 1 cases respectively for an overall response rate of 20%. Twenty-seven patients (48%) obtained progressive disease, median time to progression (TTP) was 3,6 months, median overall survival was 16 months. NF-kB was positive in 46 cases (69%). All main clinical characteristics resulted well balanced between NF-kB positive and NF-kB negative patients. Response rate was 6% (2 PR) vs 43% (8 PR and 1 CR) (p= 0.001) in NF-kB positive and NF-kB negative tumours respectively whereas progressive disease was observed in 19 (54%) vs 8 (23%) cases in NF-kB positive and NF-kB negative cases respectively. Median TTP in NF- kB positive patients was 2.9 months versus 6.8 months in the remaining NF-kB negative patients (p= 0.01). Conclusions: Both the difference in median TTP and in response rate seem to confirm that NF-kB may play a crucial role in predicting the efficacy of cetuximab therapy in advanced colorectal tumours. The analysis is ongoing and updated results on an expanded number of cases will be presented. No significant financial relationships to disclose.

Download Full-text

Utility Values in Colorectal Cancer Patients Treated with Chemotherapy

10.21203/rs.3.rs-510614/v1 ◽

2021 ◽

Author(s):

Majid Atfannezhad ◽

Mehran Sharifi ◽

Mahmood Yousefi ◽

Farzan Madadizadeh ◽

Hosein Ameri

Keyword(s):

Colorectal Cancer ◽

Income Level ◽

Advanced Stage ◽

Low Level ◽

Utility Values ◽

Education Status ◽

Female Aging ◽

The Mean ◽

The Difference ◽

Colorectal Cancer Patients

Abstract PurposeThe purpose of present study was to calculate utility values in colorectal cancer (CRC) patients by EQ-5D-5L and cTTO.MethodsThe EQ-5D-5L and cTTO were used to calculate utility values in the patients. A total of 105 patients with CRC were consecutively selected from chemotherapy ward of the Oncology Center of Omid in the second most population province, Isfahan, in Iran. The difference between mean utility values in each factor examined by the t-test and ANOWA. Finally, The BetaMix was used to identify predictors of the utility.ResultsThe mean EQ-5D-5L index and cTTO values were 0.45 ±0.03 and 0.51±0.02, respectively. The anxiety and pain were the most common problems reported by the patients. Univariate analyses showed that the difference between the mean EQ-5D-5L index values were significant for age, education status, income level, stage of cancer, and comorbidity number; also, showed that the difference between the mean cTTO values were significant for age, income level, employment status, stage of cancer, and comorbidity number. The BetaMix showed that lower mean utility values were significantly associated with female, aging, a low level of income, a greater number of comorbidities and advanced stage of cancer.ConclusionThe factors of female, aging, a low level of income, advanced stage of cancer, and a greater number of comorbidities should be considered for improving values of utility. In addition, focusing on anxiety/depression through financial and social supports can be critical for the improvement in the quality of life in the patients.

Download Full-text